A High-Density Admixture Map for Disease Gene Discovery in African Americans
Open accessAbstract
Admixture mapping (also known as "mapping by admixture linkage disequilibrium," or MALD) provides a way of localizing genes that cause disease, in admixed ethnic groups such as African Americans, with approximately 100 times fewer markers than are required for whole-genome haplotype scans. However, it has not been possible to perform powerful scans with admixture mapping because the method requires a dense map of validated markers known to have large frequency differences between Europeans and Africans. To create such a map, we screened through databases containing approximately 450000 single-nucleotide polymorphisms (SNPs) for which frequencies had been estimated in African and European population samples. We experimentally confirmed the frequencies of the most promising SNPs in a multiethnic panel of unrelated samples and identified 3011 as a MALD map (1.2 cM average spacing). We estimate that this map is approximately 70% informative in differentiating African versus European origins of chromosomal segments. This map provides a practical and powerful tool, which is freely available without restriction, for screening for disease genes in African American patient cohorts. The map is especially appropriate for those diseases that differ in incidence between the parental African and European populations.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The paper's estimates of mean African ancestry in 23andMe African Americans are 73% or 75%, unlike previous estimates that typically ranged from 77% to 93%.
“Unlike previous estimates of the mean proportion of African ancestry, which typically have ranged from 77% to 93% African ancestry,2–4,48–62 our estimates, depending on exclusions, are 73% or 75%.”
From The genetic ancestry of African Americans, Latinos, and European Americans across the United States (2015) · cites this paper as [4]
The Results report 20% mean European ancestry in 109 African American samples, implying approximately 80% African ancestry—one previous estimate within the cited 77%–93% range. The paper does not establish that full range or estimate ancestry in 23andMe participants. In the citing sentence, the citation is attached to the previous-estimates clause, not to the citing authors’ own 73% or 75% estimates. (LLM, conf=0.84)
Experimental — accuracy not yet measuredAfrican Americans in the US typically carry segments of DNA shaped by contributions from peoples of Europe, Africa, and the Americas, with variation in African and European admixture proportions across individuals and differences in groups across parts of the country.
“Previous studies have shown that African Americans in the US typically carry segments of DNA shaped by contributions from peoples of Europe, Africa, and the Americas, with variation in African and European admixture proportions across individuals and differences in groups across parts of the country.2–4”
From The genetic ancestry of African Americans, Latinos, and European Americans across the United States (2015) · cites this paper as [4]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredMore recent studies using high-density genotype data provide reliable individual ancestry estimates, illustrate large variability in African and European ancestry proportions at an individual level, and detect low proportions of Native American ancestry.
“More recent studies that utilized high-density genotype data provide reliable individual ancestry estimates, illustrate the large variability in African and European ancestry proportions at an individual level, and are able to detect low proportions of Native American ancestry.3–11”
From The genetic ancestry of African Americans, Latinos, and European Americans across the United States (2015) · cites this paper as [4]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Part of this paper’s reference list could not be split into single entries.
Maximum Likelihood from Incomplete Data Via the <i>EM</i> Algorithm
Dempster, A. P., Laird, N. M., & Rubin, D. B. (1977) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1977.tb01600.x · Cited by 50,444 · see citing works
The International HapMap Project
†The International HapMap Consortium, Genotyping centres: Baylor College of Medicine and ParAllele BioScience, Gibbs, R. A., Belmont, J. W., Hardenbol, P., Willis, T. D., Yu, F., Chinese HapMap Consortium, Yang, H., Ch'ang, L.-Y., et al. (2003) · Nature · doi:10.1038/nature02168 · Cited by 6,057 · see citing works
Self-citationThe Structure of Haplotype Blocks in the Human Genome
Gabriel, S. B., Schaffner, S. F., Nguyen, H., Moore, J. M., Roy, J., Blumenstiel, B., Higgins, J., DeFelice, M., Lochner, A., Faggart, M., et al. (2002) · Science · doi:10.1126/science.1069424 · Cited by 5,863 · see citing works
Self-citationUse of Unlinked Genetic Markers to Detect Population Stratification in Association Studies
Pritchard, J. K., & Rosenberg, N. A. (1999) · The American Journal of Human Genetics · doi:10.1086/302449 · Cited by 1,198 · see citing works
Estimating African American Admixture Proportions by Use of Population-Specific Alleles
Parra, E. J., Marcini, A., Akey, J., Martinson, J., Batzer, M. A., Cooper, R., Forrester, T., Allison, D. B., Deka, R., Ferrell, R. E., et al. (1998) · The American Journal of Human Genetics · doi:10.1086/302148 · Cited by 771 · see citing works
Measuring and using admixture to study the genetics of complex diseases
Halder, I., & Shriver, M. D. (2003) · Human Genomics · doi:10.1186/1479-7364-1-1-52 · Cited by 93 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [5]5. Chen M-H, Shao Q-M, Ibrahim JG (2000) Monte Carlo methods in Bayesian computation. Springer, New York
Cited by
Sorted by citations
A haplotype map of the human genome
The International HapMap Consortium (2005) · Nature · doi:10.1038/nature04226 · Cited by 5,858 · see citing works
Population Structure and Eigenanalysis
Patterson, N., Price, A. L., & Reich, D. (2006) · PLoS Genetics · doi:10.1371/journal.pgen.0020190 · Cited by 5,280 · see citing works
Self-citationMendelian randomization: Using genes as instruments for making causal inferences in epidemiology
Lawlor, D. A., Harbord, R. M., Sterne, J. A. C., Timpson, N., & Davey Smith, G. (2008) · Statistics in Medicine · doi:10.1002/sim.3034 · Cited by 4,618 · see citing works
A draft sequence of the Neandertal genome
Green, R. E., Krause, J., Briggs, A. W., Maricic, T., Stenzel, U., Kircher, M., Patterson, N., Li, H., Zhai, W., Fritz, M. H.-Y., et al. (2010) · Science · doi:10.1126/science.1188021 · Cited by 4,318 · see citing works
Self-citationGenetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease
Romeo, S., Kozlitina, J., Xing, C., Pertsemlidis, A., Cox, D., Pennacchio, L. A., Boerwinkle, E., Cohen, J. C., & Hobbs, H. H. (2008) · Nature Genetics · doi:10.1038/ng.257 · Cited by 3,416 · see citing works
The Genetic Structure and History of Africans and African Americans
Tishkoff, S. A., Reed, F. A., Friedlaender, F. R., Ehret, C., Ranciaro, A., Froment, A., Hirbo, J. B., Awomoyi, A. A., Bodo, J.-M., Doumbo, O., et al. (2009) · Science · doi:10.1126/science.1172257 · Cited by 1,573 · see citing works
Self-citationSLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans
Lamason, R. L., Mohideen, M.-A. P. K., Mest, J. R., Wong, A. C., Norton, H. L., Aros, M. C., Jurynec, M. J., Mao, X., Humphreville, V. R., Humbert, J. E., et al. (2005) · Science · doi:10.1126/science.1116238 · Cited by 1,043 · see citing works
Self-citationThe genetic ancestry of African Americans, Latinos, and European Americans across the United States
Bryc, K., Durand, E. Y., Macpherson, J. M., Reich, D., & Mountain, J. L. (2015) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2014.11.010 · Cited by 712 · see citing works
Self-citationAdmixture mapping identifies 8q24 as a prostate cancer risk locus in African-American men
Freedman, M. L., Haiman, C. A., Patterson, N., McDonald, G. J., Tandon, A., Waliszewska, A., Penney, K., Steen, R. G., Ardlie, K., John, E. M., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605832103 · Cited by 612 · see citing works
Self-citationSensitive detection of chromosomal segments of distinct ancestry in admixed populations
Price, A. L., Tandon, A., Patterson, N., Barnes, K. C., Rafaels, N., Ruczinski, I., Beaty, T. H., Mathias, R., Reich, D., & Myers, S. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000519 · Cited by 539 · see citing works
Self-citationA new approach for using genome scans to detect recent positive selection in the human genome
Tang, K., Thornton, K. R., & Stoneking, M. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050171 · Cited by 489 · see citing works
Genetic architecture: the shape of the genetic contribution to human traits and disease
Timpson, N. J., Greenwood, C. M. T., Soranzo, N., Lawson, D. J., & Richards, J. B. (2018) · Nature Reviews Genetics · doi:10.1038/nrg.2017.101 · Cited by 434 · see citing works
Demonstrating stratification in a European American population
Campbell, C. D., Ogburn, E. L., Lunetta, K. L., Lyon, H. N., Freedman, M. L., Groop, L. C., Altshuler, D., Ardlie, K. G., & Hirschhorn, J. N. (2005) · Nature Genetics · doi:10.1038/ng1607 · Cited by 444 · see citing works
Long-Range LD Can Confound Genome Scans in Admixed Populations
Price, A. L., Weale, M. E., Patterson, N., Myers, S. R., Need, A. C., Shianna, K. V., Ge, D., Rotter, J. I., Torres, E., Taylor, K. D., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.06.005 · Cited by 443 · see citing works
Self-citationThe protocols for the 10/66 dementia research group population-based research programme
Prince, M., Ferri, C. P., Acosta, D., Albanese, E., Arizaga, R., Dewey, M., Gavrilova, S. I., Guerra, M., Huang, Y., Jacob, K., et al. (2007) · BMC Public Health · doi:10.1186/1471-2458-7-165 · Cited by 357 · see citing works
Sanders, A. R., Duan, J., Levinson, D. F., Shi, J., He, D., Hou, C., Burrell, G. J., Rice, J. P., Nertney, D. A., Olincy, A., et al. (2008) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2007.07101573 · Cited by 349 · see citing works
Genome-wide scans for footprints of natural selection
Oleksyk, T. K., Smith, M. W., & O'Brien, S. J. (2010) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2009.0219 · Cited by 340 · see citing works
Self-citationDiscerning the ancestry of European Americans in genetic association studies
Price, A. L., Butler, J., Patterson, N., Capelli, C., Pascali, V. L., Scarnicci, F., Ruiz-Linares, A., Groop, L., Saetta, A. A., Korkolopoulou, P., et al. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.0030236 · Cited by 327 · see citing works
Self-citationHalder, I., Shriver, M., Thomas, M., Fernandez, J. R., & Frudakis, T. (2008) · Human Mutation · doi:10.1002/humu.20695 · Cited by 274 · see citing works
Jablonski, K. A., McAteer, J. B., de Bakker, P. I. W., Franks, P. W., Pollin, T. I., Hanson, R. L., Saxena, R., Fowler, S., Shuldiner, A. R., Knowler, W. C., et al. (2010) · Diabetes · doi:10.2337/db10-0543 · Cited by 271 · see citing works
Self-citationOrtega, V. E., & Meyers, D. A. (2014) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2013.10.040 · Cited by 237 · see citing works
Implications of correlations between skin color and genetic ancestry for biomedical research
Parra, E. J., Kittles, R. A., & Shriver, M. D. (2004) · Nature Genetics · doi:10.1038/ng1440 · Cited by 220 · see citing works
Ancestry analysis in the 11-M Madrid bomb attack investigation
Phillips, C., Prieto, L., Fondevila, M., Salas, A., Gómez-Tato, A., Álvarez-Dios, J., Alonso, A., Blanco-Verea, A., Brión, M., Montesino, M., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006583 · Cited by 149 · see citing works
Conti, D. V., Lee, W., Li, D., Liu, J., Van Den Berg, D., Thomas, P. D., Bergen, A. W., Swan, G. E., Tyndale, R. F., Benowitz, N. L., et al. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn181 · Cited by 136 · see citing works
Population differences of two coding SNPs in pigmentation-related genes SLC24A5 and SLC45A2
Soejima, M., & Koda, Y. (2006) · International Journal of Legal Medicine · doi:10.1007/s00414-006-0112-z · Cited by 128 · see citing works
Shriner, D. (2013) · Current Protocols in Human Genetics · doi:10.1002/0471142905.hg0123s76 · Cited by 111 · see citing works
Florez, J. C., Price, A. L., Campbell, D., Riba, L., Parra, M. V., Yu, F., Duque, C., Saxena, R., Gallego, N., Tello-Ruiz, M., et al. (2009) · Diabetologia · doi:10.1007/s00125-009-1412-x · Cited by 106 · see citing works
“[26], from which these markers were selected).”
Self-citationKidd, J. M., Gravel, S., Byrnes, J., Moreno-Estrada, A., Musharoff, S., Bryc, K., Degenhardt, J. D., Brisbin, A., Sheth, V., Chen, R., et al. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2012.08.025 · Cited by 95 · see citing works
Self-citationRacial admixture and its impact on BMI and blood pressure in African and Mexican Americans
Tang, H., Jorgenson, E., Gadde, M., Kardia, S. L. R., Rao, D. C., Zhu, X., Schork, N. J., Hanis, C. L., & Risch, N. (2006) · Human Genetics · doi:10.1007/s00439-006-0175-4 · Cited by 87 · see citing works
Generalized Analysis of Molecular Variance
Nievergelt, C. M., Libiger, O., & Schork, N. J. (2007) · PLoS Genetics · doi:10.1371/journal.pgen.0030051 · Cited by 80 · see citing works
Optimal selection of SNP markers for disease association studies.
Halldórsson, B. V., Istrail, S., & De La Vega, F. M. (2004) · Human Heredity · doi:10.1159/000083546 · Cited by 65 · see citing works
Self-citationJoint testing of genotype and ancestry association in admixed families
Tang, H., Siegmund, D. O., Johnson, N. A., Romieu, I., & London, S. J. (2010) · Genetic Epidemiology · doi:10.1002/gepi.20520 · Cited by 48 · see citing works
Wang, H., Haiman, C. A., Kolonel, L. N., Henderson, B. E., Wilkens, L. R., Le Marchand, L., & Stram, D. O. (2010) · Human Genetics · doi:10.1007/s00439-010-0841-4 · Cited by 45 · see citing works
Cheng, C.-Y., Reich, D., Haiman, C. A., Tandon, A., Patterson, N., Elizabeth, S., Akylbekova, E. L., Brancati, F. L., Coresh, J., Boerwinkle, E., et al. (2012) · PLoS ONE · doi:10.1371/annotation/52e53d8e-a4bd-4419-951a-75ddcbaf6c5d · Cited by 2 · see citing works
Self-citation
- Authors
- Smith, M. W., Patterson, N., Lautenberger, J. A., Truelove, A. L., McDonald, G. J., Waliszewska, A., Kessing, B. D., Malasky, M. J., Scafe, C., Le, E., De Jager, P. L., Mignault, A. A., Yi, Z., de Thé, G., Essex, M., Sankalé, J.-L., Moore, J. H., Poku, K., Phair, J. P., Goedert, J. J., Vlahov, D., Williams, S. M., Tishkoff, S. A., Winkler, C. A., De La Vega, F. M., Woodage, T., Sninsky, J. J., Hafler, D. A., Altshuler, D., Gilbert, D. A., O’Brien, S. J., & Reich, D.
- Affiliations
- National Cancer Institute (US)
- Broad Institute (US)
- Harvard University (US)
- Vanderbilt University (US)
- University of Ghana (GH)
- Northwestern University (US)
- New York Academy of Medicine (US)
- University of Maryland, College Park (US)
- Corresponding author
- Reich, David
- ORCID
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2004-05
- Volume
- 74
- Issue
- 5
- Pages
- 1001-1013
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC1181963
- OpenAlex
- W2001115778
- Cited by
- 459
- References
- 6
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 3 · 2023: 7 · 2022: 4 · 2021: 3 · 2020: 5 · 2019: 5 · 2018: 6 · 2017: 14 · 2016: 10 · 2015: 23 · 2014: 28 · 2013: 25 · 2012: 50
- FWCI
- 20.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- NSUWorks (Nova Southeastern University) (submittedVersion)
- University Libraries (University of Maryland) (submittedVersion)
- Digital Repository at the University of Maryland (University of Maryland College Park)
- Funders
- National Institutes of Health (n01co12400-79-0-22)
- U.S. Public Health Service (N01C012400)
- National Heart, Lung, and Blood Institute (HL-65234, R01HL065234)
- National Human Genome Research Institute (K01HG002758, K-01 HG002758-01)
- National Cancer Institute (N01-CO-012400)
- National Institute of Allergy and Infectious Diseases (U19 AI50864, U19AI050864)
- National Institute of Neurological Disorders and Stroke (K08NS046341)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- admixture mapping, African Americans, admixed populations, disease gene discovery, single nucleotide polymorphisms
- MeSH terms
- Alleles, Black or African American, Chromosome Mapping, Ethnicity, Gene Frequency, Genetic Markers, Genetics, Population, Haplotypes, Humans, Linkage Disequilibrium, Genome, Human, Microsatellite Repeats, Polymorphism, Single Nucleotide, Genetic Diseases, Inborn, White People
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
